Ebbing Jan, Seibert Felix S, Pagonas Nikolaos, Bauer Frederic, Miller Kurt, Kempkensteffen Carsten, Günzel Karsten, Bachmann Alexander, Seifert Hans H, Rentsch Cyrill A, Ardelt Peter, Wetterauer Christian, Amico Patrizia, Babel Nina, Westhoff Timm H
University Hospital Basel, Department of Urology, Basel, Switzerland.
Charité - University Hospital, Campus Benjamin Franklin, Department of Urology, Berlin, Germany.
PLoS One. 2016 Jan 8;11(1):e0146395. doi: 10.1371/journal.pone.0146395. eCollection 2016.
Urinary calprotectin has been identified as a promising biomarker for acute kidney injury. To date, however, the time-dependent changes of this parameter during acute kidney injury remain elusive. The aim of the present work was to define the time-course of urinary calprotectin secretion after ischaemia/reperfusion-induced kidney injury in comparison to neutrophil gelatinase-associated lipocalin, thereby monitoring the extent of tubular damage in nephron sparing surgery for kidney tumours.
The study population consisted of 42 patients. Thirty-two patients underwent either open or endoscopic nephron sparing surgery for kidney tumours. During the surgery, the renal arterial pedicle was clamped with a median ischaemic time of 13 minutes (interquartile range, 4.5-20.3 minutes) in 26 patients. Ten retro-peritoneoscopic living donor nephrectomy patients and 6 nephron sparing surgery patients in whom the renal artery was not clamped served as controls. Urinary calprotectin and neutrophil gelatinase-associated lipocalin concentrations were repeatedly measured by enzyme-linked immunosorbent assay and assessed according to renal function parameters.
Urinary concentrations of calprotectin and neutrophil gelatinase-associated lipocalin increased significantly after ischaemia/reperfusion injury, whereas concentrations remained unchanged after nephron sparing surgery without ischaemia/reperfusion injury and after kidney donation. Calprotectin and neutrophil gelatinase-associated lipocalin levels were significantly increased 2 and 8 hours, respectively, post-ischaemia. Both proteins reached maximal concentrations after 48 hours, followed by a subsequent persistent decrease. Maximal neutrophil gelatinase-associated lipocalin and calprotectin concentrations were 9-fold and 69-fold higher than their respective baseline values. The glomerular filtration rate was only transiently impaired at the first post-operative day after ischaemia/reperfusion injury (p = 0.049).
Calprotectin and neutrophil gelatinase-associated lipocalin can be used to monitor clinical and sub-clinical tubular damage after nephron sparing surgery for kidney tumours. Urinary calprotectin concentrations start rising within 2 hours after ischaemia/reperfusion-induced kidney injury.
尿钙卫蛋白已被确定为急性肾损伤的一种有前景的生物标志物。然而,迄今为止,该参数在急性肾损伤期间随时间的变化仍不明确。本研究的目的是确定缺血/再灌注诱导的肾损伤后尿钙卫蛋白分泌的时间进程,并与中性粒细胞明胶酶相关脂质运载蛋白进行比较,从而监测肾肿瘤保留肾单位手术中肾小管损伤的程度。
研究人群包括42例患者。32例患者接受了开放性或内镜下肾肿瘤保留肾单位手术。手术期间,26例患者的肾动脉蒂被夹闭,中位缺血时间为13分钟(四分位间距,4.5 - 20.3分钟)。10例后腹腔镜活体供肾切除术患者和6例未夹闭肾动脉的保留肾单位手术患者作为对照。通过酶联免疫吸附测定法反复测量尿钙卫蛋白和中性粒细胞明胶酶相关脂质运载蛋白浓度,并根据肾功能参数进行评估。
缺血/再灌注损伤后,尿钙卫蛋白和中性粒细胞明胶酶相关脂质运载蛋白浓度显著升高,而在未发生缺血/再灌注损伤的保留肾单位手术及肾移植术后,浓度保持不变。缺血后2小时和8小时,钙卫蛋白和中性粒细胞明胶酶相关脂质运载蛋白水平分别显著升高。两种蛋白在48小时后达到最大浓度,随后持续下降。中性粒细胞明胶酶相关脂质运载蛋白和钙卫蛋白的最大浓度分别比各自的基线值高9倍和69倍。缺血/再灌注损伤后的术后第一天,肾小球滤过率仅短暂受损(p = 0.049)。
钙卫蛋白和中性粒细胞明胶酶相关脂质运载蛋白可用于监测肾肿瘤保留肾单位手术后的临床和亚临床肾小管损伤。缺血/再灌注诱导的肾损伤后2小时内,尿钙卫蛋白浓度开始升高。